Preparation method of brexpiprazole tablet

Abstract

The invention discloses a preparation method of a brexpiprazole tablet, and belongs to the field of pharmacy, and the brexpiprazole tablet comprises the following components: brexpiprazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose and sodium stearyl fumarate. By controlling specific parameters in combination with operation steps in the preparation method, the medicine with good product quality can be produced, the product quality is stable, and the content of related substances is low.

Description

Technical Field

[0001] The invention relates to a method for preparing a medicine, in particular to a method for preparing brepazole tablets, and belongs to the field of pharmaceuticals. Background Art

[0002] Brepiraazole is an antipsychotic drug used to treat schizophrenia. Brepiraazole works by regulating the function of dopamine D2 receptors and can improve symptoms such as psychomotor retardation and emotional apathy in patients with schizophrenia. The drug can block dopamine D2 receptors and reduce abnormal neurotransmission caused by their overactivation. The use of brepiraazole can relieve positive symptoms in schizophrenia, such as hallucinations and delusions, as well as negative symptoms such as emotional flatness and social withdrawal.

[0003] Brepiraazole tablets are prepared from raw material Brepiraazole and its auxiliary materials by tableting process, through process parameters and formulation ratio. At present, Brepiraazole tablets are prone to tablet disintegration and low product quality stability during the production and preparation process, which affects product quality. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a method for preparing brepazine tablets, which solves the problem of easy disintegration of tablets in the production process of the prior art.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0006] A method for preparing brepirazole tablets, comprising: brepirazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, sodium stearyl fumarate, and a film coating premix; wherein the weight ratio of brepirazole: lactose: corn starch: microcrystalline cellulose: low-substituted hydroxypropyl cellulose: hydroxypropyl cellulose: sodium stearyl fumarate: film coating premix is ​​0.5-2: 46.4-47.9: 15-25: 5-15: 5-15: 1.2-3.4: 0.4-0.8: 3.14-4.14;

[0007] The preparation method of breprazol tablets comprises the following steps:

[0008] S1. Premixing: Weigh the prescribed amount of lactose, corn starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and add them to the wet granulator in sequence for mixing;

[0009] S2. Granulation:

[0010] S21. Preparation of adhesive: Weigh hydroxypropyl cellulose and slowly add it to purified water and stir continuously to completely dissolve it, set aside;

[0011] S22. Add liquid: Turn on the stirring and cutting knife, add the adhesive, add liquid manually, the adding time is 120-180s, and after the addition is completed, continue granulation for 25-35s, stop the machine to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0012] S23. Primary granulation: Turn on the stirring and cutting blades, continue granulation for 55-75 seconds, stop the machine to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0013] S24. Secondary granulation: Turn on the stirring and cutting knife, continue granulation for 55-75s, and discharge;

[0014] S25. Wet granulation: The soft material is moved to the swing granulator for wet granulation;

[0015] S3. Drying: Add the wet granules into the fluidized bed for drying. When the material temperature reaches 45±5°C, turn off the heating, use an infrared moisture meter to measure the moisture content, control the moisture content to ≤3.0%, and stop the machine to discharge the material;

[0016] S4. Dry granulation: Add the dried material to the swing granulator for dry granulation;

[0017] S5. Total mixing: The dry whole granules and the prescribed amount of sodium stearyl fumarate are sequentially added to the mixer for total mixing;

[0018] S6. Tableting: Tablets are pressed according to the prescribed tablet weight, with a weight difference of ±6.5%, to obtain brexpiprazole tablets.

[0019] Furthermore, in step S1, the premixing control parameters are: stirring speed 140-180 rpm, cutter speed 1000-1400 rpm, mixing time 8-15 min.

[0020] Furthermore, in step S2, the liquid adding control parameters are: stirring speed 140-180 rpm, and cutting knife speed 1000-1400 rpm.

[0021] Furthermore, in step S2, the primary granulation control parameters are: stirring speed 140-180 rpm, and cutter speed 1000-1400 rpm.

[0022] Furthermore, in step S2, the secondary granulation control parameters are: stirring speed 110-150 rpm, and cutter speed 1000-1400 rpm.

[0023] Furthermore, in step S2, the mesh number of the sieve used for wet granulation is a 16-mesh stainless steel sieve.

[0024] Furthermore, in step S3, the drying parameters are as follows: the air inlet temperature is set to 70±10°C, and the air volume is set to 22.5Hz.

[0025] Furthermore, in step S4, the mesh number of the sieve used for dry granulation is a 24-mesh stainless steel sieve.

[0026] Furthermore, in step S5, the overall mixing parameters are: stirring speed 8-15 rpm, mixing time 4-8 min.

[0027] Furthermore, in step S6, the tableting parameters are as follows: the average hardness is controlled to be 30-50N, and the friability is ≤1.0%.

[0028] Due to the adoption of the above technical solution, the technical progress achieved by the present invention is:

[0029] The brepazole tablets produced by the preparation method of the present invention have high product quality, high stability and low related substances. Firstly, by mixing and preparing the components according to the proportion of weight, the material binding force between the tablets can be better exerted, so that the prepared medicine has good stability; secondly, by controlling the mixing parameters in the preparation process, including the coordination between the stirring speed, the cutting knife speed and the mixing time, the components can be evenly dispersed and combined, and have good dispersion uniformity; finally, the secondary granulation method is adopted to granulate, so that the obtained molecular particles have good uniformity and enhanced solubility. DETAILED DESCRIPTION

[0030] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] The present invention is further described in detail below in conjunction with embodiments:

[0032] A method for preparing brepirazole tablets, comprising: brepirazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, sodium stearyl fumarate, and a film coating premix; wherein the weight ratio of brepirazole: lactose: corn starch: microcrystalline cellulose: low-substituted hydroxypropyl cellulose: hydroxypropyl cellulose: sodium stearyl fumarate: film coating premix is ​​0.5-2: 46.4-47.9: 15-25: 5-15: 5-15: 1.2-3.4: 0.4-0.8: 3.14-4.14.

[0033] The preparation method of breprazol tablets comprises the following steps:

[0034] S1. Premixing: Weigh the prescribed amount of lactose, corn starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and add them to the wet granulator in sequence for mixing; parameters: stirring speed 140-180rpm, cutter speed 1000-1400rpm, mixing time 8-15min;

[0035] S2. Granulation:

[0036] S21. Preparation of adhesive: Weigh hydroxypropyl cellulose and slowly add it to purified water and stir continuously to completely dissolve it, set aside;

[0037] S22. Add liquid: start stirring and cutting, parameters: stirring speed 140-180rpm, cutting speed 1000-1400rpm, add binder, adding time 120-180s, continue granulation for 25-35s after adding liquid, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0038] S23. Primary granulation: start stirring and cutting, parameters: stirring speed 140-180rpm, cutting speed 1000-1400rpm, continue granulation for 55-75s, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0039] S24. Secondary granulation: Turn on stirring and cutting knife, parameters: stirring speed 110-150rpm, cutting knife speed 1000-1400rpm, continue granulation 55-75s, discharge;

[0040] S25. Wet granulation: The soft material is moved to a swing granulator and wet granulated using a 16-mesh stainless steel screen;

[0041] S3. Drying: Add the wet granules into the fluidized bed for drying. Drying parameters: Set the air inlet temperature to 70±10℃, set the air volume to 22.5Hz, wait until the material temperature reaches 45±5℃, turn off the heating, use an infrared moisture meter to measure the moisture, control the moisture to ≤3.0%, and stop the machine to discharge;

[0042] S4. Dry granulation: The dried material is added to a swing granulator and dry granulated using a 24-mesh stainless steel sieve;

[0043] S5. Total mixing: The dry whole granules and the prescribed amount of sodium stearyl fumarate were sequentially added to the mixer, mixing parameters: stirring speed 8-15rpm, mixing time 4-8min;

[0044] S6. Tabletting: Tableting is performed according to the weight of the prescribed tablets, using a 6 mm round punch die, tabletting parameters: average hardness is controlled to be 30-50 N, friability is ≤ 1.0%, weight difference is ± 6.5%, and brexpiprazole tablets are obtained by tableting.

[0045] The setting parameters of the infrared moisture meter are: temperature 105℃, time 3min.

[0046] Example 1

[0047] A method for preparing brepirazole tablets, the composition of which includes: brepirazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, and sodium stearyl fumarate;

[0048] The preparation method of breprazol tablets comprises the following steps:

[0049] S1. Premixing: Weigh the prescribed amount of lactose, corn starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and add them to the wet granulator in sequence for mixing; parameters: stirring speed 180 rpm, cutter speed 1400 rpm, mixing for 15 min;

[0050] S2. Granulation:

[0051] S21. Preparation of adhesive: Weigh hydroxypropyl cellulose and slowly add it to purified water and stir continuously to completely dissolve it, set aside;

[0052] S22. Add liquid: start stirring and cutting, parameters: stirring speed 180rpm, cutting speed 1400rpm, add binder, adding time 180s, continue granulation for 35s after adding liquid, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0053] S23. Primary granulation: start stirring and cutting, parameters: stirring speed 180rpm, cutting speed 1400rpm, continue granulation for 75s, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0054] S24. Secondary granulation: Turn on stirring and cutting knife, parameters: stirring speed 150rpm, cutting knife speed 1400rpm, continue granulation for 75s, discharge;

[0055] S25. Wet granulation: The soft material is moved to a swing granulator and wet granulated using a 16-mesh stainless steel screen;

[0056] S3. Drying: Add the wet granules into the fluidized bed for drying. Drying parameters: Set the air inlet temperature to 70±10℃, set the air volume to 22.5Hz, wait until the material temperature reaches 45±5℃, turn off the heating, use an infrared moisture meter to measure the moisture, control the moisture to ≤3.0%, and stop the machine to discharge;

[0057] S4. Dry granulation: The dried material is added to a swing granulator and dry granulated using a 24-mesh stainless steel sieve;

[0058] S5. Total mixing: The dry whole granules and the prescribed amount of sodium stearyl fumarate were sequentially added to the mixer, mixing parameters: stirring speed 15 rpm, mixing time 8 min;

[0059] S6. Tabletting: Tableting is performed according to the weight of the prescribed tablets, using a 6 mm round punch die, tabletting parameters: average hardness is controlled to be 30-50 N, friability is ≤ 1.0%, weight difference is ± 6.5%, and brexpiprazole tablets are obtained by tableting.

[0060] The setting parameters of the infrared moisture meter are: temperature 105℃, time 3min.

[0061] Example 2

[0062] A method for preparing brepirazole tablets, the composition of which includes: brepirazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, and sodium stearyl fumarate;

[0063] The preparation method of breprazol tablets comprises the following steps:

[0064] S1. Premixing: Weigh the prescribed amount of lactose, corn starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and add them to the wet granulator in sequence for mixing; parameters: stirring speed 160 rpm, cutter speed 1200 rpm, mixing for 10 min;

[0065] S2. Granulation:

[0066] S21. Preparation of adhesive: Weigh hydroxypropyl cellulose and slowly add it to purified water and stir continuously to completely dissolve it, set aside;

[0067] S22. Add liquid: start stirring and cutting, parameters: stirring speed 160rpm, cutting speed 1200rpm, add adhesive, add liquid manually, adding time 150s, continue granulation for 30s after adding liquid, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0068] S23. Primary granulation: start stirring and cutting, parameters: stirring speed 160rpm, cutting speed 1200rpm, continue granulation for 60s, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0069] S24. Secondary granulation: Turn on stirring and cutting knife, parameters: stirring speed 130rpm, cutting knife speed 1200rpm, continue granulation for 60s, discharge;

[0070] S25. Wet granulation: The soft material is moved to a swing granulator and wet granulated using a 16-mesh stainless steel screen;

[0071] S3. Drying: Add the wet granules into the fluidized bed for drying. Drying parameters: Set the air inlet temperature to 70±10℃, set the air volume to 22.5Hz, wait until the material temperature reaches 45±5℃, turn off the heating, use an infrared moisture meter to measure the moisture, control the moisture to ≤3.0%, and stop the machine to discharge;

[0072] S4. Dry granulation: The dried material is added to a swing granulator and dry granulated using a 24-mesh stainless steel sieve;

[0073] S5. Total mixing: The dry whole granules and the prescribed amount of sodium stearyl fumarate were sequentially added to the mixer, mixing parameters: stirring speed 10 rpm, mixing time 5 min;

[0074] S6. Tabletting: Tableting is performed according to the weight of the prescribed tablets, using a 6 mm round punch die, tabletting parameters: average hardness is controlled to be 30-50 N, friability is ≤ 1.0%, weight difference is ± 6.5%, and brexpiprazole tablets are obtained by tableting.

[0075] The setting parameters of the infrared moisture meter are: temperature 105℃, time 3min.

[0076] Example 3

[0077] A method for preparing brepirazole tablets, the composition of which includes: brepirazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, and sodium stearyl fumarate;

[0078] The preparation method of breprazol tablets comprises the following steps:

[0079] S1. Premixing: Weigh the prescribed amount of lactose, corn starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and add them to the wet granulator in sequence for mixing; parameters: stirring speed 140 rpm, cutter speed 1000 rpm, mixing for 8 min;

[0080] S2. Granulation:

[0081] S21. Preparation of adhesive: Weigh hydroxypropyl cellulose and slowly add it to purified water and stir continuously to completely dissolve it, set aside;

[0082] S22. Add liquid: start stirring and cutting, parameters: stirring speed 140rpm, cutting speed 1000rpm, add binder, adding time 120s, continue granulation for 25s after adding liquid, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0083] S23. Primary granulation: start stirring and cutting, parameters: stirring speed 140rpm, cutting speed 1000rpm, continue granulation for 55s, stop to clean the material on the wall of the wet granulator, and observe the state of the soft material;

[0084] S24. Secondary granulation: Turn on stirring and cutting knife, parameters: stirring speed 110rpm, cutting knife speed 1000rpm, continue granulation for 55s, discharge;

[0085] S25. Wet granulation: The soft material is moved to a swing granulator and wet granulated using a 16-mesh stainless steel screen;

[0086] S3. Drying: Add the wet granules into the fluidized bed for drying. Drying parameters: Set the air inlet temperature to 70±10℃, set the air volume to 22.5Hz, wait until the material temperature reaches 45±5℃, turn off the heating, use an infrared moisture meter to measure the moisture, control the moisture to ≤3.0%, and stop the machine to discharge;

[0087] S4. Dry granulation: The dried material is added to a swing granulator and dry granulated using a 24-mesh stainless steel sieve;

[0088] S5. Total mixing: The dry whole granules and the prescribed amount of sodium stearyl fumarate were sequentially added to the mixer, mixing parameters: stirring speed 8 rpm, mixing time 4 min;

[0089] S6. Tabletting: Tableting is performed according to the weight of the prescribed tablets, using a 6 mm round punch die, tabletting parameters: average hardness is controlled to be 30-50 N, friability is ≤ 1.0%, weight difference is ± 6.5%, and brexpiprazole tablets are obtained by tableting.

[0090] The setting parameters of the infrared moisture meter are: temperature 105℃, time 3min.

[0091] The above is the production and preparation process of Example 1, Example 2, and Example 3, wherein the prescription dosage of Example 1, Example 2, and Example 3 is shown in the following table:

[0092] Table 1: Summary of prescription quantities of Examples 1-3

[0093] project Example 1 Example 2 Example 3 Brepiraazole 2.0g 1.0g 0.5g lactose 47.9g 47.4g 46.4g Corn starch 25.0g 20.0g 15.0g Microcrystalline Cellulose 15.0g 10.0g 5.0g Low substituted hydroxypropyl cellulose 15.0g 10.0g 5.0g Hydroxypropylcellulose 3.4g 1.8g 1.2g Sodium stearyl fumarate 0.8g 0.6g 0.4g Film coating premix 4.14g 3.64g 3.14g water 66.96g 66.96g 66.96g

[0094] Product quality evaluation standards for Brepiraazole Tablets:

[0095] (1) Properties: Film-coated tablets, white after removing the coating;

[0096] (2) Related substances: Impurity A ≤ 0.5%; Impurity C ≤ 0.5%; Impurity E ≤ 0.5%; Other maximum single impurities ≤ 0.5%; Total impurities ≤ 2.0%;

[0097] (3) Dissolution: should be 80% of the labeled amount;

[0098] (4) Content: Contains brepazine (C 25 H 27N3O2S) should be 95.0%-105.0% of the labeled amount.

[0099] The breprazol tablets prepared in Example 1-3 were tested for product quality, and the results are shown in the following table:

[0100] Table 2: Results of product quality testing of Examples 1-3

[0101]

[0102]

[0103] The product quality test results of Examples 1-3 all meet the requirements and are within the qualified range. Therefore, the breprazol tablets prepared in Examples 1-3 are of high quality and good quality.

[0104] Drug stability study: The brepazole tablets prepared in Example 1-3 were subjected to a 6-month accelerated stability study at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5%. The properties, related substances, dissolution, and content were tested and the changes were observed, as shown in the following table:

[0105] Table 3: Stability test results of Example 1

[0106]

[0107] Table 4: Stability test results of Example 2

[0108]

[0109] Table 5: Stability test results of Example 3

[0110]

[0111]

[0112] From the results of the stability study, the quality stability of the drugs obtained by the preparation methods of Examples 1-3 is good, and the content and related substances change steadily during the stability study period. Therefore, by comparing the results of the stability study, it can be seen that the entire process of the preparation of the embodiments of the present invention (including the prescription process, the preparation process and the production operation control) has good operability and can obtain drugs with stable quality. Specifically, by limiting the combination of the prescription process, the preparation process and the production operation control, the quality content and related substances of the drugs are controlled, and tablet drugs with good quality content stability, low related substances and good dissolution are obtained.

[0113] In summary, this embodiment confirms that the breprazol tablets obtained by the preparation method of the present invention have high product quality, good stability, low related substances and good solubility. First, by mixing and preparing the components according to the proportion of weight, the material binding force between the tablets can be better exerted, so that the prepared drug has good stability; secondly, by controlling the mixing parameters of the preparation process, including the coordination between the stirring speed, the cutting knife speed and the mixing time, the components can be evenly dispersed and combined, with good dispersion uniformity; finally, the secondary granulation method is used for granulation, so that the obtained molecular particles not only have good uniformity, but also stimulate the space between the molecular particles, so that the solubility is also enhanced.

[0114] The embodiments described above are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention, and all of them belong to the protection scope of the present invention.

Claims

1. A method for preparing breprazol tablets, characterized in that: The composition of brepirazole tablets includes: brepirazole, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, sodium stearyl fumarate, and film coating premix; wherein the weight ratio of brepirazole: lactose: corn starch: microcrystalline cellulose: low-substituted hydroxypropyl cellulose: hydroxypropyl cellulose: sodium stearyl fumarate: film coating premix is ​​0.5-2: 46.4-47.9: 15-25: 5-15: 5-15: 1.2-3.4: 0.4-0.8: 3.14-4.14; The preparation method of breprazol tablets comprises the following steps: S1. Premixing: Weigh the prescribed amount of lactose, corn starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and add them to the wet granulator in sequence for mixing; S2. Granulation: S21. Preparation of adhesive: Weigh hydroxypropyl cellulose and slowly add it to purified water and stir continuously to completely dissolve it, set aside; S22. Add liquid: Turn on the stirring and cutting knife, add the adhesive, add liquid manually, the adding time is 120-180s, and after the addition is completed, continue granulation for 25-35s, stop the machine to clean the material on the wall of the wet granulator, and observe the state of the soft material; S23. Primary granulation: Turn on the stirring and cutting blades, continue granulation for 55-75 seconds, stop the machine to clean the material on the wall of the wet granulator, and observe the state of the soft material; S24. Secondary granulation: Turn on the stirring and cutting knife, continue granulation for 55-75s, and discharge; S25. Wet granulation: The soft material is moved to the swing granulator for wet granulation; S3. Drying: Add the wet granules into the fluidized bed for drying. When the material temperature reaches 45±5°C, turn off the heating, use an infrared moisture meter to measure the moisture content, control the moisture content to ≤3.0%, and stop the machine to discharge the material; S4. Dry granulation: Add the dried material to the swing granulator for dry granulation; S5. Total mixing: The dry whole granules and the prescribed amount of sodium stearyl fumarate are sequentially added to the mixer for total mixing; S6. Tableting: Tablets are pressed according to the prescribed tablet weight, with a weight difference of ±6.5%, to obtain brexpiprazole tablets.

2. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S1, the premixing control parameters are: stirring speed 140-180 rpm, cutter speed 1000-1400 rpm, mixing time 8-15 min.

3. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S2, the liquid adding control parameters are: stirring speed 140-180 rpm, cutting knife speed 1000-1400 rpm.

4. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S2, the primary granulation control parameters are: stirring speed 140-180 rpm, and cutter speed 1000-1400 rpm.

5. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S2, the secondary granulation control parameters are: stirring speed 110-150 rpm, and cutter speed 1000-1400 rpm.

6. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S2, the mesh number of the sieve used for wet granulation is a 16-mesh stainless steel sieve.

7. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S3, the drying parameters are: the inlet air temperature is set to 70±10°C, and the air volume is set to 22.5Hz.

8. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S4, the mesh number of the sieve used for dry granulation is a 24-mesh stainless steel sieve.

9. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S5, the overall mixing parameters are: stirring speed 8-15 rpm, mixing time 4-8 min.

10. The method for preparing breprazol tablets according to claim 1, characterized in that: In step S6, the tableting parameters are as follows: the average hardness is controlled to be 30-50N, and the friability is ≤1.0%.

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